Polylysine and polyornithine are known and are under investigation as DNA condensing agents to be used in non-viral gene therapy. However, as is known in the literature, poly-L-lysine has cytotoxic effects that decrease with decreasing molecular weight. Thus, preparation of a low molecular weight polylysine is desirable.
Poly-L-lysine and other polyamino acids have been prepared by a variety of routes. Commercially, poly-L-lysine has been prepared by reaction of Nε-carbobenzyloxy(Cbz)-L-Lysine, N-carboxyanhydride with a polymerization initiator to produce poly-Nε-Cbz-L-lysine. The poly-Nε-Cbz-L-lysine is treated with hydrobromic acid in acetic acid to remove the Cbz group and form poly-L-lysine having a molecular weight of about 7,000 Daltons. The product can be dialyzed, lyophilized, and recovered in an 11-30% yield. This yield of the current process is variable and is unacceptably low. Thus, a need exists for higher yield large-scale processes having less variability to produce polylysine having a lysine-basis weight average molecular weight from about 5,500 Daltons to about 12,000 Daltons.